JP3285265B2 - Fluorescence observation device - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a fluorescence observation apparatus capable of obtaining an observation image by ordinary illumination light and a fluorescence image by excitation light.

[0002]

2. Description of the Related Art In recent years, autofluorescence from a living body or a drug is injected into a living body, the fluorescence of the drug is detected as a two-dimensional image, and a disease state such as degeneration of living tissue or cancer (for example, There are technologies for diagnosing the type of disease and the extent of invasion.

When a living tissue is irradiated with light, fluorescence having a longer wavelength than the light (excitation light) is generated. Examples of a fluorescent substance in a living body include NADH (nicotinamide adenine nucleotide), FMN (flavin mononucleotide), and pyridine nucleotide. Recently, the correlation between such endogenous substances and diseases has become clear. In addition, HpD (hematoporphyrin), Ph
otofrin, ALA (δ-amino levul
Inic acid) has the property of accumulating in cancer, and is used for diagnosis of a disease site by injecting this into a living body and observing the fluorescence of the substance.

[0004] Since the above-mentioned fluorescence is extremely weak, it is necessary to take an extremely sensitive image to observe the fluorescence. This high-sensitivity shooting
Intensifiers are well known. Recently, a method has been proposed in which two-dimensional synchronous detection is performed as shown in FIG. 12 to increase the sensitivity.

[0005] First, a continuous laser beam is irradiated from a laser device 201, and the laser beam is chopped at a high speed by a chopper 202 at a 1/600 S clock generated by a clock generator 220, and enlarged by a concave lens 203. 2
Irradiate No. 04. The fluorescence from the tissue 204 is applied to the lens 2
05, The image is captured by the CCD 207 through the filter 206.

The filter 206 is a band-pass filter that cuts a laser beam and passes only a longer wavelength, that is, only a fluorescent light. At this time, the fluorescence is generated in synchronization with the blinking of the excitation light, and this is
That is, detection is performed in synchronization with the period of 1 / 600S. Then, this is converted into an image signal by the video processor 208 and further converted into digital data by the A / D converter 209.

The multiplexer 210 switches this data at the timing of the clock 1 / 600S, and the frame of ODD and EVEN, that is, when fluorescence is generated,
The images when they do not occur (or vice versa) are stored in the frame memories 211 and 212, respectively. The data stored in the frame memories 211 and 212 is divided by 1/30
The difference is made by the difference circuit 213 at a period of 0S (the clock is divided by the frequency dividing circuit 214), and the noise is canceled by integrating the difference by, for example, about ten times by the integrating circuit 215, and a necessary signal is obtained. Is amplified, and as a result, S / N can be improved.

This is displayed on a monitor 217 as a video signal by a video processor 216. Incidentally, in FIG.
2 shows a two-dimensional lock-in amplifier unit for improving / N.

On the other hand, in the fluorescence observation, in addition to the fluorescence image,
Observing a normal screen is also important in performing orientation and the like. Conventionally, a plurality of cameras have been used to capture both a fluorescent image and a normal image, or the same camera has been captured in a time-division manner.

[0010]

When a fluorescent image and a normal image are photographed by different cameras, the structure becomes complicated and the photographed portion becomes large. In addition, when photographing is performed by one camera in a time-division manner, there is a problem that the fluorescent light image is darkened, the normal image is halated, and in the worst case, the image is burned because the fluorescent light and the light receiving intensity of the normal image are extremely different.

SUMMARY OF THE INVENTION The present invention has been made in view of the above points, and is capable of photographing both a fluorescent image and a normal image with a simple structure without burning or the like by one camera. It is an object to provide a fluorescence observation device.

[0012]

SUMMARY OF THE INVENTION A first fluorescent light according to the present invention
The observation device switches illumination between normal illumination light and excitation light in order.
Illumination means for emitting light, and illumination light is emitted from the illumination means.
Image of the reflected light from the subject when
When excitation light is emitted from the stage, the fluorescence from the subject
Imaging means for imaging light; and excitation light by the illumination means.
The irradiation time is longer than the irradiation time of the illumination light by the same illumination means
Switching between illumination light and excitation light by the same illumination means
Timing control means for controlling the timing
It is characterized by that. Also, the second fluorescent lamp according to the present invention is provided.
The illumination device switches between normal illumination light and excitation light
Illumination means, and illumination light is emitted from the illumination means.
The reflected light from the subject is imaged when the
When the excitation light is irradiated from the
Imaging means for imaging the image, and imaging taken by the imaging means
Integrating means for integrating a signal; and
The number of integrations when imaging fluorescence based on
From the number of integrations when imaging reflected light based on bright light
Integral controlling the number of integrations of the integrating means so as to increase
And a number control means.

[0013]

Embodiments of the present invention will be described below with reference to the drawings. 1 to 3 relate to a first embodiment of the present invention, FIG. 1 shows a configuration of a fluorescence observation apparatus of the first embodiment, and FIG. 2 shows an example of a fluorescence intensity distribution in a case of a normal part and a lesion part. FIG. 3 is a timing chart for explaining the operation of the first embodiment. The first embodiment is an apparatus for detecting both a fluorescence image and an observation image in a time-division manner with a common image sensor.

A fluorescence observation apparatus 1 of the first embodiment shown in FIG. 1 includes a light source device 2 for generating illumination light for normal observation and excitation light for fluorescence observation, and a tissue 3 to be an object to be observed.
An image pickup device 4 for picking up a normal image and a fluorescent image, a two-dimensional lock-in amplifier 5 for amplifying an image detected by the image pickup device 4 and improving S / N, and dividing the image into a normal image and a fluorescent image. An image processing device 6 for processing and synthesizing each image; a timing controller 7 for synchronously controlling the light source device 2, the imaging device 4, the two-dimensional lock-in amplifier 5, and the image processing device 6; It is composed of a monitor 8 for displaying an image passed through the device 6.

The light source device 2 has a wavelength of λ 0 (for example, λ
A laser 9 (for example, an excimer laser, a krypton laser, a He-Cd laser, or a dye laser can be used) which generates excitation light (0 = 350 mm to 500 mm) (abbreviated as excitation light λ0 for simplicity); The laser light is arranged so that a peripheral portion extends on the optical path,
The light-shielding disk is provided with irregularities on the periphery thereof so as to blink at a cycle of 720S, and is driven to rotate, and a xenon lamp 11 that generates illumination light for observing a normal image.
A first rotary filter 12 that is arranged on the optical path of the illumination light, has R, B, and G color filters, and is rotated by, for example, 1 / 30S by a motor (not shown); The rotary shutter 13 is disposed on the optical path of the laser light in synchronism with the optical path of the laser light and transmits and blocks the laser light (rotated at 1 / 30S).
A dichroic mirror 14 that is disposed at an angle to the optical path of the laser beam and that reflects only the excitation light λ 0, and is disposed on the optical path in front of the dichroic mirror 14 and And an illumination lens 15 for irradiating light to the side. That is, the light source device 2 alternately emits the pulsed laser light as the excitation light and the R, G, and B illumination light.

The image pickup device 4 includes an objective lens 16 for forming an optical image of the tissue 3, and is disposed on an optical path of the objective lens 16.
Fluorescent image (fluorescence of λ1, λ2 longer wavelength than λ0) rotated by 1 / 30S by motor (not shown) so as to synchronize with
A second filter 17 for passing a normal image, a CCD 18 as an image sensor for taking the fluorescence and the normal image in a time-shared manner, and a video processor 19 for driving the CCD 18 and converting it to an image signal. And

The video processor 19 and the second filter 17 are controlled by the timing controller 7, and the video processor 19 is, for example, 1/1/2 of 1 / 2720S.
An image signal of one frame is generated at a high speed of 440S.

A two-dimensional lock-in amplifier 5 synchronizes with an A / D converter 20 for converting the image signal into digital data and the timing controller 7, and converts each image data into a frame in accordance with the blinking of the excitation light of the laser 9. Memory (ODD) 22a and frame memory (E
VEN) 22b, a frame memory (ODD) 22a, and a frame memory (EVE).
N) 22b is subtracted, noise is canceled and S / N
Circuit 23 and S / N by integrating so as to accumulate images in which noise has been canceled (integrating so as to accumulate the same image portions).
And an integrating circuit 24 for amplifying the current. In addition, in the case of normal light, directly without going through the frame memory and the difference circuit,
The signal is input to the integration circuit 24.

The image processing device 6 synchronizes the amplified normal and fluorescent image data with the timing controller 7 to store a normal image storage frame memory (comprising an RGB frame memory) 25 and a λ1 image storage frame memory. A multiplexer 28 for separating the image into a frame memory 27 for storing the .lambda.2 image, and a frame memory 26 for storing the .lambda.1 image and a .lambda.2
The arithmetic circuit 29 controls the frame memory 27 for image storage, the superimpose circuit 30 for synthesizing the image of the frame memory 26 for normal image storage and the image of the arithmetic circuit 29, and controls the superimpose circuit 30 and the timing controller 7. And a computer 31 that performs the operations.

Next, the operation of this embodiment will be described. First,
For example, the excitation light λ0 pulsed at a cycle of 1 / 720S from the light source device 2 and the observation light (R,
G, B), the tissue 3 is irradiated alternately in a time sharing manner.

FIG. 3 shows a chopper 10 and a rotary shutter 1.
3, timings of the first filter 12 and the second filter 17 are shown. The rotary shutter 13 and the first filter 12 are alternately opened, and the second filter 17 is synchronized with the rotary shutter 13 and the first filter 12, that is, the rotary shutter 13 is opened to transmit the excitation light to the tissue 3. When irradiating the tissue 3, the filters of λ1 and λ2 are sequentially arranged on the observation optical path, and when irradiating the tissue 3 with the normal light (R, G, B),
The filter has been removed. Further, the excitation light is blinked by the chopper 10 at 1 / 720S.

More specifically, the rotary shutter 1
3 is open for a period of 2/3 of the 1 / 30S period as shown in FIG. 3A, and during this period, the first filter 12 becomes a light shielding portion (shown closed) as shown in FIG. 3B. , FIG. 3 (d)
The laser light is turned on and off by the chopper 10 that opens and closes as shown in (1), and the rotary shutter 13 passes the pulsed excitation light λ0 (in this period, the first filter 12 becomes a light shielding portion,
R, G, and B light are blocked). This excitation light λ 0 is reflected by the dichroic mirror 14 and passes through the lens 15 to the tissue 3.
To emit fluorescent light longer than the excitation light λ0.

The wavelength component of this fluorescence transmitted through the second rotary filter 17 by the objective lens 16 reaches the CCD 18 and forms a fluorescence image. As shown in FIG. 3 (c), the wavelengths .lambda.1 and .lambda.2 of the second rotating filter 17 are sequentially arranged in the imaging optical path, and the fluorescent images of the wavelengths .lambda.1 and .lambda.2 are imaged in 1 / 90S.

During the next 1/3 of the 1 / 30S period, the rotary shutter 13 is a light shielding period for shielding the laser light,
During the light-shielding period, one of the R, G, and B color filters is sequentially arranged in the optical path of the first filter 12, and one of the R, G, and B illumination lights (for example, R illumination light) is output, and the dichroic light is output. The light passes through the mirror 14 and is irradiated on the tissue 3 via the lens 15.

For example, the R illumination light reflected by the tissue 3 is transmitted through the second rotary filter 17 by the objective lens 16,
An R image is formed on the CCD 18. As shown in FIG. 3C, in this period, the second rotary filter 17 is in a state where the opening portion is arranged in the imaging optical path (in FIG. 3C, it is shown without a (filter)). . At the same timing in the next cycle, illumination and imaging with G illumination light are performed, and in the next cycle, illumination and imaging with B illumination light are performed. That is,
In accordance with the excitation light and the illumination light in a time-division manner, imaging is performed in a time-division manner by the imaging device 4 having the built-in CCD 18.

Thus, the wavelengths λ1 and λ2 of the fluorescence
, And a 1 /
The signal is converted into an image signal in synchronization with the period of 1 / 1440S, which is half of the period of 720S, that is, in synchronization with the blinking of the excitation light. In addition,
The R, G, and B illuminations are continuously illuminated by 1 / 90S, but are read out repeatedly at a period of 1 / 1440S.

The two-dimensional lock-in amplifier 5 improves the S / N and amplifies the high-speed image signal as described above. In particular, in the case of a fluorescent image, the difference circuit 23 performs difference processing on the blinking image and the blinking image when blinking, thereby greatly reducing the influence of noise irrelevant to blinking or 1 / f noise which increases particularly at low frequencies. Thus, a fluorescent image signal with a good S / N can be generated even in the case of a weak fluorescent image.

Therefore, the fluorescent image signal output from the difference circuit 23 can be set to a level that does not become extremely unbalanced from the level of the image signal for normal observation. In other words, the signal levels of the fluorescent image and the normal image can be matched to some extent by passing through the two-dimensional lock-in amplifier 5,
In order to increase the level of the fluorescent image, there is no need to provide a circuit that greatly increases the gain in the signal processing system.
In such a case, it is possible to effectively prevent the occurrence of halation or burn-in which often occurs on the image side.

However, the brightness (intensity) of the fluorescence depends on the intensity of the laser beam, the type of the fluorescent agent, the efficiency of the generation of the fluorescence, and the like.
Changes, the integration circuit 24 changes according to the brightness of the observed image.
The amplification factor may be changed by the integration number of times or the processing by the digital window (the number of bits increases according to the integration number, and the gain is changed depending on which part of the data is cut out of this data).

The image signal thus amplified is divided into a fluorescent image and a normal image by an image processing device 6, each of which is processed, converted into image data suitable for display, and further synthesized by a superimpose circuit 30. , On the monitor 8.

FIG. 2 shows the fluorescence characteristics when irradiated with the excitation light λ0. For example, the intensity of the fluorescence of the tissue obtained by the excitation light of 442 mm is strong in the normal part, and is weaker in the lesion part than the normal part on the shorter wavelength side. That is, the wavelengths λ1, λ
In FIG. 2, since the ratio of the fluorescence intensity differs between the case of the normal part and the case of the lesion part, the lesion part and the normal part can be distinguished by calculating the ratio of the fluorescence intensity at λ1 and λ2.

Therefore, the frame memory 26 for storing the image picked up at the wavelength λ 1 and the frame memory 27 for storing the image picked up at the wavelength λ 2 are stored in the arithmetic circuit 29.
In each of the corresponding image portions, an operation for obtaining a difference is performed, and it is determined whether or not the value obtained by the difference processing is equal to or less than a set value. Outputs a color signal that is easy to identify, and allows the normal image to be identified by color in a normal image via the superimposing circuit 30 with the possibility of a lesion being below a set value.

On the other hand, in the case of an image exceeding the set value, for example, both images taken at wavelengths λ1 and λ2 are added and output to the superimpose circuit 30, and the fluorescent image is superimposed so as to be arranged in a normal image. Then, two images are displayed on the monitor 8.

Of course, the display may be performed in the same manner when the value is equal to or less than the set value, and the area equal to or less than the set value may be displayed in a color that can be easily identified. Further, a function of selecting and displaying a normal image and an image of one wavelength or displaying two fluorescent images side by side may be provided.

According to the first embodiment, the fluorescent image and the normal image can be captured by the common CCD 18, and the S / N of the fluorescent image can be reduced by passing through the two-dimensional lock-in amplifier 5. Since it is possible to greatly improve and reduce the imbalance with the signal level of the normal image, it is possible to display both images by eliminating the occurrence of burn-in and the like.

Further, since both a fluorescent image and a normal image can be photographed with a simple structure, both functions of good orientation and high-sensitivity fluorescence observation are provided, and more accurate diagnosis and observation can be performed.

Further, since the image pickup section and the signal processing system can be commonly used, a device which can handle both images can be realized at low cost. In the first embodiment, the CCD 18 has been described.
A solid-state imaging device other than a CD, such as CMD, SIT, or MOS, may be used.

Next, a second embodiment of the present invention will be described. FIG.
FIG. 8 to FIG. 8 relate to a second embodiment of the present invention, FIG. 4 shows a configuration of a fluorescence observation apparatus of the second embodiment, FIG. 5 shows an operation explanatory view, and FIG. 6 shows an example of light source selecting means. FIG. 7 shows another example of the light source selecting means, and FIG. 8 shows a specific example of the wavelength selecting means. This embodiment shows an example in which the number of integrations is controlled according to the brightness of the fluorescent image and the normal image.

The fluorescent image becomes extremely darker than the normal image, and the brightness of the fluorescent light varies depending on the excitation wavelength, the difference in the intensity, the autofluorescence and the fluorescence by the drug, the type of the drug, and the like. In the present embodiment, as described above, the brightness of the fluorescent image changes, and even if the ratio of the brightness to the normal image changes, both images are displayed well.

The fluorescence observation apparatus 40 of this embodiment includes a laser 41 for generating excitation light and a lamp 42 for generating normal illumination light.
A light source selecting means 43 for appropriately selecting the excitation light or the illumination light; and an imaging element 45 for irradiating the above-mentioned light to the living tissue 3 and detecting the reflected light (normal) or the fluorescent light as an image through the objective lens 44. (Eg CCD, CMD, SIT)
And a wavelength selecting means 46 for selecting the reflected light or the fluorescent light.
A driver 47 for driving the image sensor 45 at a high speed of, for example, 30 to 2,000 frames / S; a control circuit 48 for controlling the light source selector 43 and the wavelength selector 46 and the driver 47 in synchronization; An A / D converter 49 for converting to digital data, an integrator 50 for integrating this digital data, and a first image memory 51 and a second image memory 52 for storing the fluorescent image by the fluorescence and the normal image by the reflected light. A multiplexer 53 for sorting, and a superimposing circuit 54 for synthesizing images in the image memories 51 and 52.
And a monitor 55 for displaying it.

First, the excitation light by the laser 41 and the lamp 42
Is appropriately selected by the light source selecting means 43. Wavelengths (for example, λ1, λ2 shown in FIG.
, The illumination light as it is) is selected by the wavelength selecting means 46 and received by the image sensor 45. After the A / D conversion, the integration is performed by an integrator 50 in accordance with the brightness of the fluorescent light and the normal image, and the fluorescent image is distributed to the first image memory 51 and the normal image is distributed to the second image memory 52. Pause circuit 5
In step 4, the images are combined and displayed on the monitor 55.

FIG. 5 shows the timing of the embodiment of FIG.
First, the image sensor 45 is driven at a high speed of, for example, 180 frames / S. If the sensitivity of the fluorescence image is increased by a factor of 5 with respect to the observed image, the irradiation time ratio between the laser and the illumination light (indicated by Xe) is set to 5: 1 as shown in FIG. In contrast, by integrating the fluorescent image for five frames, the sensitivity of the fluorescent image can be improved. Note that W in FIG. 5 indicates illumination light for a normal image.

FIG. 6 shows an example of the wavelength selecting means 43. As shown in FIG. 6A, the surface of the rotatable rotary plate 56 is arranged at a certain angle with respect to the optical axis so that the optical axes of the laser 41 and the lamp 42 coincide with each other. This rotating plate 56 is similar to that shown in FIG.
A transmission window 57 partially transmitting light as shown in FIG.
There are reflecting mirrors 58 for reflecting light, each of which has a projection 59.
The opening angle of the transmission window 57 is changed in conjunction with.

That is, while the rotating plate 56 is rotated by the stepping motor 60, the projecting portion 59 is moved by the groove 62 attached to the microstage 61, and the angle of the transmission window is changed, so that the ratio of the excitation light to the illumination light is changed. Can be changed. After being set to an appropriate ratio, the groove 62 is retracted so that the protrusion 59 is not engaged.

FIG. 7 shows another example of the wavelength selecting means 43. Electronic shutter 6 in front of laser 41 and lamp 42
3 and 64 are arranged, and one of the electronic shutters 64 is provided with an inverting circuit 65. By controlling the inversion of the two electronic shutters 63 and 64, light can be emitted alternately. This light is guided to the same optical path by the dichroic mirror 66.

FIG. 8 shows a specific example of the wavelength selecting means 46.
As shown in FIG. 8A, the wavelength selecting means 46 includes a cut filter 67 for cutting the excitation light, a polarizing plate 68, and a TN.
Liquid crystal filter 71 composed of cell 69 and color polarizing plate 70
It is composed of

As shown in FIG. 8B, the liquid crystal filter 71
In the ON state, fluorescent light corresponding to the wavelength characteristic of the color polarizing plate is transmitted (for example, λ1 or λ2), and in the OFF state, light in all wavelength ranges is transmitted, and normal light is guided to the image sensor 45.

According to the second embodiment, even if the brightness of the fluorescent image changes, both the normal image and the fluorescent image can be displayed well. Further, the S / N can be further improved by combining the two-dimensional lock-in amplifier of the first embodiment with the second embodiment.

FIG. 9 shows a fluorescence observation endoscope device 72 according to a third embodiment in which the first and second embodiments are applied to an endoscope, for example. Fluorescence observation can be performed, and screening for lesions such as initial cancer can be performed.
The same components as those in the first and second embodiments are denoted by the same reference numerals.

The fluorescence observation endoscope device 72 includes an endoscope 73 inserted into a body cavity, a light source device 2, a two-dimensional lock-in amplifier 5, an image processing device 6, a timing controller 7, and a monitor 8 It is composed of A light guide 75 is inserted into the insertion portion 74 of the endoscope 73, and an end on the hand side thereof is connected to the light source device 2 to guide illumination light from the light source device 2.

The light source device 2 has substantially the same configuration as that of the first embodiment shown in FIG. The excitation light of the laser 9 is turned into pulse light through a chopper 10 rotated by a motor 10a,
7a, the light is reflected by the mirror surface of a rotating mirror 77b provided with a mirror portion and a transmitting portion (indicated by a dotted line in FIG. 9) on the rotating surface, and is incident on the proximal end of the light guide 75. The rotation of the rotating mirror 77b is controlled by the timing controller 7.

The light from the xenon lamp 11 is rotated by the motor 12a, passes through the RGB rotary filter 12 disposed on the optical path, and passes through the transmitting portion (of the rotating mirror 77b) at the timing when it reaches the optical path. Light guide 75
Is incident on the end on the hand side of. The light that has entered the proximal end of the light guide 75 is guided into the body cavity into which the insertion section 74 is inserted, and is further emitted from the distal end surface through the illumination lens 76 to the tissue in the body cavity.

The fluorescent light and the normal light generated from the tissue in the body cavity are supplied to the cover glass attached to the observation window at the end of the endoscope, the polarizing plate 67, the first objective lens 44a, the liquid crystal filter 71, and the second objective lens 44b. The image is formed on the image sensor 45 disposed in the distal end portion through the above-mentioned steps, and the photoelectric conversion is performed by the image sensor 45.

The image pickup device 45 is driven by a drive signal from a driver 47. The image pickup signal photoelectrically converted by the image pickup device 45 is amplified by a preamplifier 79, and thereafter, an A / D signal forming the two-dimensional lock-in amplifier 5. It is input to the converter 20 and the video processor 81 in the image processing device 6.

The video processor 81 performs signal processing on an image pickup signal in the case of normal light illumination, generates a standard video signal, and generates a superimpose circuit 30 '.
Through the monitor 8 to display a normal image.

On the other hand, the image pickup signal picked up by the fluorescent light is A
After being converted to a digital signal via the / D converter 20,
The frame memories 22a and 22b for storing the DD frame image and the EVEN frame image, the difference between them are obtained, and the difference circuit 23 is inputted to the multiplexer 28 in the image processing device 6 through the integration circuit 24 for integrating the difference output. You.

The signal selected by the multiplexer 28 is temporarily stored in the frame memories 26 and 27, and the two signals read from the frame memories 26 and 27 are operated by the operation circuit 29 to obtain the characteristics of the tissue. After converting the signal into a signal corresponding to the discrimination, the signal is converted into an analog signal by the D / A converter 82, and then a standard video signal is generated by the video processor 83 and output to the superimpose circuit 30 '.

For example, when the fluorescent image is determined to be a lesion, the fluorescent image is superimposed by a specific color signal into the superimposing circuit 3.
0 'and the fluorescent image is superimposed on the normal image and displayed, or two images are simultaneously displayed by superimposing processing such that the normal image and the fluorescent image are arranged side by side. The computer 31 controls the timing controller 7 and the superimpose circuit 30 '.

According to the fluorescence observation endoscope device 72, a fluorescence image can be displayed in addition to a normal endoscope image, and a region in which there is a possibility of a diseased tissue can be displayed so as to be easily identified. .

Accordingly, it is possible to provide a very effective means for screening for lesions such as initial cancer. In FIG. 9, for example, the rotating mirror 77b may be formed by plating or vapor-depositing aluminum or the like functioning as a mirror on the light shielding portion of the rotating shutter 13 in FIG. Further, a mirror may be provided on the plunger, and the plunger may be driven at a constant cycle to arrange the mirror in the optical path or to retract the mirror. Further, the mirror may be reciprocated by a predetermined angle to arrange the mirror in the optical path or to retract the mirror.

Further, the excitation light and the illumination light may be sequentially guided by the mirror to the light guide 75 side in a time-sharing manner, or switching may be performed manually or the like so that only one of them can be selectively guided. . In this way, fluorescence observation may be performed only when necessary. Similar functions may be provided for other embodiments.

FIGS. 10 and 11 show a system using an endoscope. In solar anastomosis by sigmoid colectomy, it is important to know the metabolism of the anastomotic site at the anastomotic site from the viewpoint of preventing suture failure. On the other hand, NADH contained in living tissue is a substance that controls oxygen metabolism, and by looking at this fluorescence, it is possible to diagnose, for example, the metabolic state of the suture. 10 and 11 show examples of measuring NADH for the above purpose.

First, a description will be given with reference to FIG. The endoscope observation system 101 includes an endoscope 102, a light source device 103, a signal processing device 104, and a monitor 105.

The light source device 103 incorporates a white light source 107, and a band-pass filter 108 for passing light for exciting NADH is provided on the illumination light path so as to be retractable by rotation of a motor 109, for example. A condenser lens 110 is disposed in front of the bandpass filter 108, and a light guide 111 attached to the light source device 103.
The illumination light is supplied to the end face near the hand.

The light guide 111 provided on the endoscope 102 is inserted through the flexible insertion portion 112, transmits white light or excitation light, and moves forward from the distal end surface attached to the illumination window at the distal end. The light is emitted and irradiates, for example, the suture portion 114 of the large intestine 113.

The reflected light or the fluorescent light of white light forms an image on the distal end surface of the image guide 116 disposed on the focal plane by the objective lens 115 attached to the observation window at the distal end. Then, by the image guide 116, an image based on the fluorescent light or an image based on the reflected light is transmitted to the rear end face on the hand side.

A cut filter 117 which faces the rear end face and cuts the excitation light, an image forming lens 118, a CCD
119 are sequentially arranged, and the signal photoelectrically converted by the CCD 119 is input to the CCU 120 in the signal processing circuit 104 and converted into a video signal. This CCU 120 also has the function of the two-dimensional lock-in amplifier 5 of FIG.

The signal processing circuit 104 includes the CCU 120
A video signal output from the CCU 120 stores a fluorescent image and a normal image,
The memory 121 includes a timing controller 122 for outputting a timing control signal for controlling the opening and closing of the band-pass filter 108 for separating fluorescence and a normal image, and a superimposing circuit 123 for combining both images. .

The operation of the endoscope system 101 is substantially the same as that of the fluorescence endoscope apparatus 72 described above, and therefore will not be described.
The effect is the same. It should be noted that a hard mirror as well as a soft mirror can be applied in almost the same manner.

Next, the endoscope system 131 shown in FIG. 11 will be described. In this example, instead of obtaining a fluorescent image, light is guided by an optical probe inserted into a channel of an endoscope, the tip of the probe is brought into contact with a suture site, and metabolism at the contact site is measured by NADH fluorescence. is there.

The endoscope system 131 includes the endoscope 13
2, a light source device 133 that supplies white illumination light to the endoscope 132, a light guide probe 135 inserted through a channel 134 of the endoscope 132, and a light guide probe 13
5, a second light source device 103 that supplies excitation light, and a detection device 13 that detects fluorescence guided by the light guide probe 135.
6, an analyzer 137 for obtaining metabolism from the fluorescence detected by the detector 136, and a display 138 showing the result. This analyzer 137 is the same as 2 in FIG.
It has the function of the dimension lock-in amplifier 5.

The endoscope 132 has an elongated and flexible insertion portion 14.
A light guide 142 is inserted into the light guide 1, and a proximal end of the light guide 142 is connected to a light source device 133, and white light from a white light source 143 is supplied through a condenser lens 144. This white light is emitted forward from the illumination window at the distal end of the insertion section 141, and is emitted to, for example, the suture section 114 side of the large intestine 113.

The light reflected on the suturing portion 114 forms an image on the distal end surface of an image guide 116 disposed on the focal plane by an objective lens 115 attached to an observation window. The image is transmitted to the rear end face by the image guide 116 and the eyepiece 1
The suture portion 114 side can be observed with the naked eye via 46.

The light guide probe 135 inserted into the channel 134 of the endoscope 132 has a near side branched into two, one of which is connected to the light source device 103 and the other of which is connected to the detection device 136.

The light source device 103 has the same configuration as that described with reference to FIG.
From the distal end surface protruding from the distal end outlet of No. 4, the guided excitation light is applied to the side of the suturing portion 114 that contacts this distal end surface. The excitation light from the suturing portion 114 is guided to the proximal side by the light guide probe 135, and is detected by the detector 147 through the cut filter 117 that cuts the excitation light. The light amount of the detected excitation light is analyzed by the analyzer 137 and the display device 13
8 is displayed.

The metabolism may be determined by measuring cytochrome using near-infrared light in addition to NADH fluorescence or measuring blood flow using a laser Doppler meter. It is to be noted that different embodiments may be configured by partially combining the above-described embodiments and the like.

[0077]

As described above, according to the present invention, the normal illumination light and the excitation light are irradiated in a time-division manner, and the observation image or the fluorescence image by the illumination light or the excitation light applied to the object is selected by the selection means. The selected image is synchronized with the light irradiation, an observation image or a fluorescent image is captured by a common image capturing unit, and the image captured by the image capturing unit is subjected to a difference processing on at least the fluorescent image by the image processing unit. And so on.
The fluorescent image and the normal image can be captured by the common image capturing means, and the S / N of the fluorescent image is greatly improved by the image processing means, so that the imbalance of the signal level with the normal image can be reduced. And the like can be prevented.

[Brief description of the drawings]

FIG. 1 is an overall configuration diagram of a fluorescence observation apparatus according to a first embodiment.

FIG. 2 is a characteristic diagram showing an example of a fluorescence intensity distribution in a normal part and a lesion part.

FIG. 3 is a timing chart for explaining the operation of the first embodiment.

FIG. 4 is an overall configuration diagram of a fluorescence observation apparatus according to a second embodiment of the present invention.

FIG. 5 is an operation explanatory diagram of the second embodiment.

FIG. 6 is an explanatory diagram showing an example of a light source selection unit.

FIG. 7 is an explanatory diagram showing another example of the light source selection unit.

FIG. 8 is an explanatory diagram showing a specific example of a wavelength selection unit.

FIG. 9 is a configuration diagram showing a configuration of a fluorescence endoscope apparatus according to a third embodiment of the present invention.

FIG. 10 is a configuration diagram of an endoscope system suitable for diagnosing a metabolic state of a suture portion.

FIG. 11 is a configuration diagram showing a modified example of FIG. 10;

FIG. 12 is an overall configuration diagram of a conventional fluorescence observation apparatus.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 ... Fluorescence observation device 2 ... Light source device 3 ... Tissue 4 ... Imaging device 5 ... Two-dimensional lock-in amplifier 6 ... Image processing device 7 ... Timing controller 8 ... Monitor 9 ... Laser 10 ... Chopper 11 ... Xenon lamp 12 ... First Filter 13 Rotating shutter 14 Dichroic mirror 16 Objective lens 17 Second filter 18 CCD 19 Video processor 21 Multiplexer 22 a, 22 b Frame memory 23 Difference circuit 24 Integration circuits 26 and 27 Frame memory 29 ... arithmetic circuit 30 ... superimpose circuit

Claims (2)

(57) [Claims] 1. A method of sequentially switching between normal illumination light and excitation light.
Illumination means for illuminating, test when the illumination light is irradiated from said illuminating means
Imaging the reflected light from the body and irradiating with excitation light from the illumination means
Imaging hand that captures fluorescence from the subject when
And the irradiation time of the excitation light by the illumination means.
Illumination means so that it is longer than the irradiation time of illumination light.
To control the switching timing between the illumination light and the excitation light.
A fluorescence observation device , comprising: an imaging control unit. 2. A method of sequentially switching between normal illumination light and excitation light.
Illumination means for illuminating, test when the illumination light is irradiated from said illuminating means
Imaging the reflected light from the body and irradiating with excitation light from the illumination means
Imaging hand that captures fluorescence from the subject when
Stage and integrating means for integrating an image signal picked up by the image pickup means
And the imaging unit is imaging fluorescence based on the excitation light.
When the number of integration times, the reflected light based on the illumination light is imaged
The integration means so as to be more than the number of integrations when
And a control unit for controlling the number of integrations .